Publications by authors named "Sandra Ceccatelli"

90 Publications

In utero exposure to dexamethasone causes a persistent and age-dependent exacerbation of the neurotoxic effects and glia activation induced by MDMA in dopaminergic brain regions of C57BL/6J mice.

Neurotoxicology 2021 Mar 15;83:1-13. Epub 2020 Dec 15.

Department of Biomedical Sciences, Section of Neuroscience, University of Cagliari, Cagliari, Italy; National Research Council of Italy, Neuroscience Institute, Cagliari, Italy.

Clinical and preclinical evidence indicates that prenatal exposure to glucocorticoids may induce detrimental effects in the offspring, including reduction in fetal growth and alterations in the CNS. On this basis, the present study investigated whether in utero exposure to high levels of glucocorticoids is a risk factor that may lead to an exacerbation of the central noxious effects induced by psychoactive drugs consumed later in life. To this end, pregnant C57BL6/J dams were treated with dexamethasone (DEX, 0.05 mg/kg per day) from gestational day 14 until delivery. Thereafter, the male offspring were evaluated to ascertain the magnitude of dopaminergic damage, astrogliosis and microgliosis elicited in the nigrostriatal tract by the amphetamine-related drug 3,4--methylenedioxymethamphetamine (MDMA, 4 × 20 mg/kg, 2 h apart, sacrificed 48 h later) administered at either adolescence or adulthood. Immunohistochemistry was performed in the substantia nigra pars compacta (SNc) and striatum, to evaluate dopaminergic degeneration by measuring tyrosine hydroxylase (TH), as well as astrogliosis and microgliosis by measuring glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1), respectively. Moreover, immunohistochemistry was used to ascertain the co-localization of IBA-1 with either the pro-inflammatory interleukin (IL) IL-1β or the anti-inflammatory IL IL-10, in order to determine the microglial phenotype. In utero administration of DEX induced dopaminergic damage by decreasing the density of TH-positive fibers in the striatum, although only in adult mice. MDMA administration induced dopaminergic damage and glia activation in the nigrostriatal tract of adolescent and adult mice. Mice exposed to DEX in utero and treated with MDMA later in life showed a more pronounced loss of dopaminergic neurons (adolescent mice) and astrogliosis (adolescent and adult mice) in the SNc, compared with control mice. These results suggest that prenatal exposure to glucocorticoids may induce an age-dependent and persistent increase in the susceptibility to central toxicity of amphetamine-related drugs used later in life.
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http://dx.doi.org/10.1016/j.neuro.2020.12.005DOI Listing
March 2021

Risk to human health related to the presence of perfluoroalkyl substances in food.

EFSA J 2020 Sep 17;18(9):e06223. Epub 2020 Sep 17.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half-lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and 'other children' showed a twofold higher exposure. Upper bound exposure was 4- to 49-fold higher than LB levels, but the latter were considered more reliable. 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1-year-old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long-term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI, which is of concern.
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http://dx.doi.org/10.2903/j.efsa.2020.6223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507523PMC
September 2020

Desipramine restores the alterations in circadian entrainment induced by prenatal exposure to glucocorticoids.

Transl Psychiatry 2019 10 17;9(1):263. Epub 2019 Oct 17.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Alterations in circadian rhythms are closely linked to depression, and we have shown earlier that progressive alterations in circadian entrainment precede the onset of depression in mice exposed in utero to excess glucocorticoids. The aim of this study was to investigate whether treatment with the noradrenaline reuptake inhibitor desipramine (DMI) could restore the alterations in circadian entrainment and prevent the onset of depression-like behavior. C57Bl/6 mice were exposed to dexamethasone (DEX-synthetic glucocorticoid analog, 0.05 mg/kg/day) between gestational day 14 and delivery. Male offspring aged 6 months (mo) were treated with DMI (10 mg/kg/day in drinking water) for at least 21 days before behavioral testing. We recorded spontaneous activity using the TraffiCage™ system and found that DEX mice re-entrained faster than controls after an abrupt advance in light-dark cycle by 6 h, while DMI treatment significantly delayed re-entrainment. Next we assessed the synchronization of peripheral oscillators with the central clock (located in the suprachiasmatic nucleus-SCN), as well as the mechanisms required for entrainment. We found that photic entrainment of the SCN was apparently preserved in DEX mice, but the expression of clock genes in the hippocampus was not synchronized with the light-dark cycle. This was associated with downregulated mRNA expression for arginine vasopressin (AVP; the main molecular output entraining peripheral clocks) in the SCN, and for glucocorticoid receptor (GR; required for the negative feedback loop regulating glucocorticoid secretion) in the hippocampus. DMI treatment restored the mRNA expression of AVP in the SCN and enhanced GR-mediated signaling by upregulating GR expression and nuclear translocation in the hippocampus. Furthermore, DMI treatment at 6 mo prevented the onset of depression-like behavior and the associated alterations in neurogenesis in 12-mo-old DEX mice. Taken together, our data indicate that DMI treatment enhances GR-mediated signaling and restores the synchronization of peripheral clocks with the SCN and support the hypothesis that altered circadian entrainment is a modifiable risk factor for depression.
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http://dx.doi.org/10.1038/s41398-019-0594-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797805PMC
October 2019

NRXN1 Deletion and Exposure to Methylmercury Increase Astrocyte Differentiation by Different Notch-Dependent Transcriptional Mechanisms.

Front Genet 2019 21;10:593. Epub 2019 Jun 21.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Controversial evidence points to a possible involvement of methylmercury (MeHg) in the etiopathogenesis of autism spectrum disorders (ASD). In the present study, we used human neuroepithelial stem cells from healthy donors and from an autistic patient bearing a bi-allelic deletion in the gene encoding for to evaluate whether MeHg would induce cellular changes comparable to those seen in cells derived from the ASD patient. In healthy cells, a subcytotoxic concentration of MeHg enhanced astroglial differentiation similarly to what observed in the diseased cells (N1), as shown by the number of GFAP positive cells and immunofluorescence signal intensity. In both healthy MeHg-treated and N1 untreated cells, aberrations in Notch pathway activity seemed to play a critical role in promoting the differentiation toward glia. Accordingly, treatment with the established Notch inhibitor DAPT reversed the altered differentiation. Although our data are not conclusive since only one of the genes involved in ASD is considered, the results provide novel evidence suggesting that developmental exposure to MeHg, even at subcytotoxic concentrations, induces alterations in astroglial differentiation similar to those observed in ASD.
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http://dx.doi.org/10.3389/fgene.2019.00593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610538PMC
June 2019

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.

EFSA J 2018 Dec 13;16(12):e05194. Epub 2018 Dec 13.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half-lives for PFOS and PFOA are about 5 years and 2-4 years, respectively. The derivation of a health-based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs.
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http://dx.doi.org/10.2903/j.efsa.2018.5194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009575PMC
December 2018

Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food.

EFSA J 2018 Nov 20;16(11):e05333. Epub 2018 Nov 20.

The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL-PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre- and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO-TEQ/g fat in blood sampled at age 9 years based on PCDD/F-TEQs. No association was observed when including DL-PCB-TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F-TEQ only was on average 2.4- and 2.7-fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL-PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.
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http://dx.doi.org/10.2903/j.efsa.2018.5333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009407PMC
November 2018

Spinal cord injury in zebrafish induced by near-infrared femtosecond laser pulses.

J Neurosci Methods 2019 01 31;311:259-266. Epub 2018 Oct 31.

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address:

Background: The spinal cord is composed of a large number of cells that interact to allow the organism to function. To perform detail studies of cellular processes involved in spinal cord injury (SCI), one must use repeatable and specific methods to target and injure restricted areas of the spinal cord.

New Method: We propose a robust method to induce SCI in zebrafish by laser light. With a 2-photon microscope equipped with a femtosecond near-infrared pump laser, we explored the effects of laser beam exposure time, area, and intensity to induce precise and repeatable SCI with minimized collateral damage to neighboring cells.

Results: Through behavioral studies in zebrafish larvae, we assessed the functional outcome of intensive laser light directed at the spinal cord. Our experiments revealed that a laser pulse with wavelength 800 nm, duration 2.6 ms, and light intensity 390 mW was sufficient to induce controlled cell death in a single cell or a spinal cord segment. Collateral damage was observed if cells were exposed to laser pulses exceeding 470 mW. With these settings, we could induce precise and repeatable SCI in zebrafish larvae, resulting in loss of motor and sensory function.

Comparison With Existing Method(s): Our method offers a simple and more controlled setting to induce SCI in zebrafish. We describe how the near-infrared femtosecond laser should be adjusted for achieving optimal results with minimal collateral damage.

Conclusions: We present a precise and robust method for inducing SCI in zebrafish with single-cell resolution using femtosecond near-infrared laser pulses.
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http://dx.doi.org/10.1016/j.jneumeth.2018.10.035DOI Listing
January 2019

Risk to human and animal health related to the presence of 4,15-diacetoxyscirpenol in food and feed.

EFSA J 2018 Aug 16;16(8):e05367. Epub 2018 Aug 16.

4,15-Diacetoxyscirpenol (DAS) is a mycotoxin primarily produced by fungi and occurring predominantly in cereal grains. As requested by the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed the risk of DAS to human and animal health related to its presence in food and feed. Very limited information was available on toxicity and on toxicokinetics in experimental and farm animals. Due to the limitations in the available data set, human acute and chronic health-based guidance values (HBGV) were established based on data obtained in clinical trials of DAS as an anticancer agent (anguidine) after intravenous administration to cancer patients. The CONTAM Panel considered these data as informative for the hazard characterisation of DAS after oral exposure. The main adverse effects after acute and repeated exposure were emesis, with a no-observed-adverse-effect level (NOAEL) of 32 μg DAS/kg body weight (bw), and haematotoxicity, with a NOAEL of 65 μg DAS/kg bw, respectively. An acute reference dose (ARfD) of 3.2 μg DAS/kg bw and a tolerable daily intake (TDI) of 0.65 μg DAS/kg bw were established. Based on over 15,000 occurrence data, the highest acute and chronic dietary exposures were estimated to be 0.8 and 0.49 μg DAS/kg bw per day, respectively, and were not of health concern for humans. The limited information for poultry, pigs and dogs indicated a low risk for these animals at the estimated DAS exposure levels under current feeding practices, with the possible exception of fattening chicken. Assuming similar or lower sensitivity than for poultry, the risk was considered overall low for other farm and companion animal species for which no toxicity data were available. In consideration of the similarities of several trichothecenes and the likelihood of co-exposure via food and feed, it could be appropriate to perform a cumulative risk assessment for this group of substances.
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http://dx.doi.org/10.2903/j.efsa.2018.5367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009455PMC
August 2018

Update: methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin.

EFSA J 2018 Jul 24;16(7):e05332. Epub 2018 Jul 24.

EFSA was asked by the European Commission to update the Scientific Opinion on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances in food of animal origin. This guidance document presents a simple and pragmatic approach which takes into account both analytical and toxicological considerations. The RPA shall be based on the reasonably achievable lowest residue concentration that can unequivocally be determined by official control laboratories, i.e. the reasonably achievable lowest decision limit (CCα). The aim is to check whether this concentration is low enough to adequately protect the consumers of food commodities that contain that substance. The proposed step-wise approach applies toxicological screening values (TSVs), based on genotoxic potential, pharmacological activity, as well as other effects of the substance. The highest dietary exposure corresponding to the reasonably achievable lowest CCα for the substance has to be estimated and compared with the TSV. Where equal to or lower than the TSV, the reasonably achievable lowest CCα can be accepted as the RPA. If higher, the sensitivity of the analytical method needs to be improved. In the case where no further analytical improvements are feasible within a short to medium time frame, a substance-specific risk assessment should be considered. This also applies when the potential adverse effects do not allow use of the decision tree, as for high potency carcinogens, inorganic substances or compounds with allergenic effects or causing blood dyscrasias. The CONTAM Panel concluded that RPAs should be food matrix independent. RPAs cannot be applied to non-edible matrices, which are also monitored for non-allowed pharmacologically active substances.
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http://dx.doi.org/10.2903/j.efsa.2018.5332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009670PMC
July 2018

Paraquat and Maneb Exposure Alters Rat Neural Stem Cell Proliferation by Inducing Oxidative Stress: New Insights on Pesticide-Induced Neurodevelopmental Toxicity.

Neurotox Res 2018 Nov 1;34(4):820-833. Epub 2018 Jun 1.

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Pesticide exposure has been linked to the pathogenesis of neurodevelopmental and neurodegenerative disorders including autism spectrum disorders, attention deficit/hyperactivity, and Parkinson's disease (PD). Developmental exposure to pesticides, even at low concentrations not harmful for the adult brain, can lead to neuronal loss and functional deficits. It has been shown that prenatal or early postnatal exposure to the herbicide paraquat (PQ) and the fungicide maneb (MB), alone or in combination, causes permanent toxicity in the nigrostriatal dopamine system, supporting the idea that early exposure to these pesticides may contribute to the pathophysiology of PD. However, the mechanisms mediating PQ and MB developmental neurotoxicity are not yet understood. Therefore, we investigated the neurotoxic effect of low concentrations of PQ and MB in primary cultures of rat embryonic neural stem cells (NSCs), with particular focus on cell proliferation and oxidative stress. Exposure to PQ alone or in combination with MB (PQ + MB) led to a significant decrease in cell proliferation, while the cell death rate was not affected. Consistently, PQ + MB exposure altered the expression of major genes regulating the cell cycle, namely cyclin D1, cyclin D2, Rb1, and p19. Moreover, PQ and PQ + MB exposures increased the reactive oxygen species (ROS) production that could be neutralized upon N-acetylcysteine (NAC) treatment. Notably, in the presence of NAC, Rb1 expression was normalized and a normal cell proliferation pattern could be restored. These findings suggest that exposure to PQ + MB impairs NSCs proliferation by mechanisms involving alterations in the redox state.
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http://dx.doi.org/10.1007/s12640-018-9916-0DOI Listing
November 2018

Risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed.

EFSA J 2018 May 25;16(5):e05242. Epub 2018 May 25.

Fumonisins, mycotoxins primarily produced by and , occur predominantly in cereal grains, especially in maize. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to fumonisins and their modified and hidden forms in feed. Fumonisin B (FB ), FB and FB are the most common forms of fumonisins in feedstuffs and thus were included in the assessment. FB , FB and FB have the same mode of action and were considered as having similar toxicological profile and potencies. For fumonisins, the EFSA Panel on Contaminants in the Food Chain (CONTAM) identified no-observed-adverse-effect levels (NOAELs) for cattle, pig, poultry (chicken, ducks and turkeys), horse, and lowest-observed-adverse-effect levels (LOAELs) for fish (extrapolated from carp) and rabbits. No reference points could be identified for sheep, goats, dogs, cats and mink. The dietary exposure was estimated on 18,140 feed samples on FB representing most of the feed commodities with potential presence of fumonisins. Samples were collected between 2003 and 2016 from 19 different European countries, but most of them from four Member States. To take into account the possible occurrence of hidden forms, an additional factor of 1.6, derived from the literature, was applied to the occurrence data. Modified forms of fumonisins, for which no data were identified concerning both the occurrence and the toxicity, were not included in the assessment. Based on mean exposure estimates, the risk of adverse health effects of feeds containing FB was considered very low for ruminants, low for poultry, horse, rabbits, fish and of potential concern for pigs. The same conclusions apply to the sum of FB and their hidden forms, except for pigs for which the risk of adverse health effect was considered of concern.
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http://dx.doi.org/10.2903/j.efsa.2018.5242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009563PMC
May 2018

Update of the Scientific Opinion on opium alkaloids in poppy seeds.

EFSA J 2018 May 16;16(5):e05243. Epub 2018 May 16.

Poppy seeds are obtained from the opium poppy L.). They are used as food and to produce edible oil. The opium poppy plant contains narcotic alkaloids such as morphine and codeine. Poppy seeds do not contain the opium alkaloids, but can become contaminated with alkaloids as a result of pest damage and during harvesting. The European Commission asked EFSA to provide an update of the Scientific Opinion on opium alkaloids in poppy seeds. The assessment is based on data on morphine, codeine, thebaine, oripavine, noscapine and papaverine in poppy seed samples. The CONTAM Panel confirms the acute reference dose (ARfD) of 10 μg morphine/kg body weight (bw) and concluded that the concentration of codeine in the poppy seed samples should be taken into account by converting codeine to morphine equivalents, using a factor of 0.2. The ARfD is therefore a group ARfD for morphine and codeine, expressed in morphine equivalents. Mean and high levels of dietary exposure to morphine equivalents from poppy seeds considered to have high levels of opium alkaloids (i.e. poppy seeds from varieties primarily grown for pharmaceutical use) exceed the ARfD in most age groups. For poppy seeds considered to have relatively low concentrations of opium alkaloids (i.e. primarily varieties for food use), some exceedance of the ARfD is also seen at high levels of dietary exposure in most surveys. For noscapine and papaverine, the available data do not allow making a hazard characterisation. However, comparison of the dietary exposure to the recommended therapeutical doses does not suggest a health concern for these alkaloids. For thebaine and oripavine, no risk characterisation was done due to insufficient data. However, for thebaine, limited evidence indicates a higher acute lethality than for morphine and the estimated exposure could present a health risk.
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http://dx.doi.org/10.2903/j.efsa.2018.5243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009406PMC
May 2018

Risks to human and animal health related to the presence of moniliformin in food and feed.

EFSA J 2018 Mar 2;16(3):e05082. Epub 2018 Mar 2.

Moniliformin (MON) is a mycotoxin with low molecular weight primarily produced by fungi and occurring predominantly in cereal grains. Following a request of the European Commission, the CONTAM Panel assessed the risk of MON to human and animal health related to its presence in food and feed. The limited information available on toxicity and on toxicokinetics in experimental and farm animals indicated haematotoxicity and cardiotoxicity as major adverse health effects of MON. MON causes chromosome aberrations but no genotoxicity data and no carcinogenicity data were identified. Due to the limitations in the available toxicity data, human acute or chronic health-based guidance values (HBGV) could not be established. The margin of exposure (MOE) between the no-observed-adverse-effect level (NOAEL) of 6.0 mg/kg body weight (bw) for cardiotoxicity from a subacute study in rats and the acute upper bound (UB) dietary exposure estimates ranged between 4,000 and 73,000. The MOE between the lowest benchmark dose lower confidence limit (for a 5% response - BMDL) of 0.20 mg MON/kg bw per day for haematological hazards from a 28-day study in pigs and the chronic dietary human exposure estimates ranged between 370 and 5,000,000 for chronic dietary exposures. These MOEs indicate a low risk for human health but were associated with high uncertainty. The toxicity data available for poultry, pigs, and mink indicated a low or even negligible risk for these animals from exposure to MON in feed at the estimated exposure levels under current feeding practices. Assuming similar or lower sensitivity as for pigs, the CONTAM Panel considered a low or even negligible risk for the other animal species for which no toxicity data suitable for hazard characterisation were identified. Additional toxicity studies are needed and depending on their outcome, the collection of more occurrence data on MON in food and feed is recommended to enable a comprehensive human risk assessment.
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http://dx.doi.org/10.2903/j.efsa.2018.5082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009678PMC
March 2018

Appropriateness to set a group health-based guidance value for fumonisins and their modified forms.

EFSA J 2018 Feb 23;16(2):e05172. Epub 2018 Feb 23.

The EFSA Panel on Contaminants in the Food Chain (CONTAM) established a tolerable daily intake (TDI) for fumonisin B (FB ) of 1.0 μg/kg body weight (bw) per day based on increased incidence of megalocytic hepatocytes found in a chronic study with mice. The CONTAM Panel considered the limited data available on toxicity and mode of action and structural similarities of FB and found it appropriate to include FB , FB and FB in a group TDI with FB . Modified forms of FBs are phase I and phase II metabolites formed in fungi, infested plants or farm animals. Modified forms also arise from food or feed processing, and include covalent adducts with matrix constituents. Non-covalently bound forms are not considered as modified forms. Modified forms of FBs identified are hydrolysed FB (HFB ), partially hydrolysed FB (pHFB ), -(carboxymethyl)-FB (NCM-FB ), -(1-deoxy-d-fructos-1-yl)-FB (NDF-FB ), -fatty acyl FB , -fatty acyl FB and -palmitoyl-HFB . HFB , pHFB , NCM-FB and NDF-FB show a similar toxicological profile but are less potent than FB . Although data shows that -fatty acyl FBs are more toxic than FB , no data were available for -fatty acyl FBs and -fatty acyl FBs. The CONTAM Panel concluded that it was not appropriate to include modified FBs in the group TDI for FB . The uncertainty associated with the present assessment is high, but could be reduced provided more data are made available on occurrence, toxicokinetics and toxicity of FB and modified forms of FB .
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http://dx.doi.org/10.2903/j.efsa.2018.5172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009576PMC
February 2018

Assessment of a decontamination process for dioxins and PCBs from fish meal by replacement of fish oil.

EFSA J 2018 Feb 12;16(2):e05174. Epub 2018 Feb 12.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process of fish meal. It consisted of extraction of the fish oil, filtration and adsorption with activated carbon, and replacement with decontaminated fish oil in order to reduce the amount of dioxins (polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)), and dioxin-like (DL-) and non-dioxin-like (NDL-) polychlorinated biphenyls (PCBs). All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Data provided by the feed business operator were assessed for efficacy of the process and to demonstrate that the process did not adversely affect the characteristics and the nature of the product. The process was effective in removing PCDD/Fs (97%) and DL- and NDL-PCBs (93%). The fish meal produced complied with EU regulations for these contaminants. The Panel considered that the reference to information available in published literature was a pragmatic approach to demonstrate that the replacement of fish oil and the use of activated carbon to adsorb these contaminants does not lead to any detrimental changes in the nature of the fish meal. However, it was noted that the process could deplete some beneficial constituents (e.g. oil-soluble vitamins). Information was provided to demonstrate the safe disposal of the waste material. The CONTAM Panel concluded that on the basis of the information submitted by the feed business operator the proposed decontamination process to remove dioxins (PCDD/Fs) and PCBs from the fish meal by oil extraction followed by replacement with decontaminated fish oil, was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.
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http://dx.doi.org/10.2903/j.efsa.2018.5174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009759PMC
February 2018

Assessment of a decontamination process for dioxins and PCBs from fish meal by hexane extraction and replacement of fish oil.

EFSA J 2018 Feb 12;16(2):e05173. Epub 2018 Feb 12.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process for fish meal. This process entails solvent (hexane) extraction of fish oil from fish meal to remove dioxins (polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) as well as dioxin-like (DL-) and non-dioxin-like (NDL-) polychlorinated biphenyls (PCBs) followed by replacement with decontaminated fish oil. All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. The data provided by the feed business operator were assessed with respect to the efficacy of the process, absence of solvent residues, and on information demonstrating that the process does not adversely affect the nature and characteristics of the product. According to data provided, the process was effective in removing PCDD/Fs and DL-PCBs by approximately 70% and NDL-PCBs by about 60%. The data showed that it is possible to meet the current EU requirements with respect to these contaminants, provided that the level of contamination of untreated fish meal is within the range of the tested batches. It is unlikely that hazardous substances (i.e. hexane) remain in the final product. The Panel considered that there is no evidence that fish oil extraction followed by replacement with decontaminated fish oil leads to detrimental changes in the nutritional composition of the fish meal, although some beneficial constituents (e.g. lipophilic vitamins) might be depleted. The feed business operator submitted information to demonstrate safe disposal of the waste material. The CONTAM Panel concluded that the proposed decontamination process to remove dioxins (PCDD/Fs) and PCBs from fish meal by means of solvent extraction and fish oil replacement was assessed to be compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.
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http://dx.doi.org/10.2903/j.efsa.2018.5173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009502PMC
February 2018

Effect on public health of a possible increase of the maximum level for 'aflatoxin total' from 4 to 10 μg/kg in peanuts and processed products thereof, intended for direct human consumption or use as an ingredient in foodstuffs.

EFSA J 2018 Feb 8;16(2):e05175. Epub 2018 Feb 8.

EFSA was asked to deliver a scientific opinion regarding the effect on public health of a possible increase of the maximum level (ML) for 'aflatoxin total' (AFT; sum of aflatoxin B1, aflatoxin B2, aflatoxin G1 and aflatoxin G2) from 4 to 10 μg/kg in peanuts and processed products thereof. Aflatoxins are genotoxic and cause hepatocellular carcinomas in humans. The Panel on Contaminants in the Food Chain (CONTAM Panel) evaluated 8,085 samples of peanuts and 472 samples of peanut butter, with > 60% left-censored. The mean concentration of AFT in peanuts was 2.65/3.56 μg/kg (lower bound (LB)/upper bound (UB)) with a maximum of 1,429 μg/kg. The mean concentration in peanut butter was 1.47/1.92 μg/kg (LB/UB) with a maximum of 407 μg/kg. Peanut oil was not included since all data were left-censored and the ML does not apply for oil. Exposure was calculated for a 'Current ML' and 'Increased ML' scenario, and mean chronic exposure estimates for consumers only, amounted to 0.04-2.74 ng/kg body weight (bw) per day and 0.07-4.28 ng/kg bw per day, respectively. The highest exposures were calculated for adolescents and other children. The CONTAM Panel used the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives for the risk characterisation. Under the scenario of the current ML, the cancer risk was estimated to range between 0.001 and 0.213 aflatoxin-induced cancers per 100,000 person years. Under the scenario of the increased ML, it ranged between 0.001 and 0.333 aflatoxin-induced cancers per 100,000 person years. Comparing these data calculated under the current ML scenario with the yearly excess cancer risk of 0.014 shows a higher risk for consumers of peanuts and peanut butter in some surveys. The calculated cancer risks indicate that an increase of the ML would further increase the risk by a factor of 1.6-1.8.
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http://dx.doi.org/10.2903/j.efsa.2018.5175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009717PMC
February 2018

Update of the risk assessment on 3-monochloropropane diol and its fatty acid esters.

EFSA J 2018 Jan 10;16(1):e05083. Epub 2018 Jan 10.

The CONTAM Panel updated the assessment of the risks for human health related to the presence of 3-monochloropropane diol (3-MCPD) and its fatty acid esters in food published in 2016 in view of the scientific divergence identified in the establishment of the tolerable daily intake (TDI) in the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (FAO/WHO) report published in 2017. In this update, dose-response analysis was performed following the recent EFSA Scientific Committee guidance on the use of benchmark dose (BMD) approach in risk assessment, and a review of available data on developmental and reproduction toxicity was included. The outcome of this review indicates that in rats short-term exposure to 3-MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity. Decreased sperm count and histopathological changes in the testis and epididymis were observed following longer treatment periods at higher doses. Regarding increased incidence kidney tubular hyperplasia, BMD analysis using model averaging resulted in a BMDL of 0.20 mg/kg bw per day in male rats, which was selected as the new Reference Point (RP) for renal effects. For the effects on male fertility, decreased sperm motility was selected as the most sensitive relevant endpoint and a BMDL of 0.44 mg/kg bw per day was calculated. The RP for renal effects was considered to derive an updated group TDI of 2 μg/kg bw per day for 3-MCPD and its fatty acid esters and was considered protective also for effects on male fertility. The established TDI of 2 μg/kg bw per day is not exceeded in the adult population. A slight exceedance of the TDI was observed in the high consumers of the younger age groups and in particular for the scenarios on infants receiving formula only.
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http://dx.doi.org/10.2903/j.efsa.2018.5083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009698PMC
January 2018

Assessment of decontamination processes for dioxins and dioxin-like PCBs in fish oil by physical filtration with activated carbon.

EFSA J 2017 Dec 20;15(12):e05081. Epub 2017 Dec 20.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of decontamination processes involving the adsorption with activated carbon and physical filtration of fish oil in order to reduce the amount of dioxins (polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) and dioxin-like polychlorinated biphenyls (DL-PCBs). All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. Two feed business operators provided data on their respective decontamination processes, which were assessed in terms of the efficacy of the process and the absence of adverse effects in the nature and characteristics of the product after decontamination. The processes proved to be able to remove PCDD/Fs (82-95%) and DL-PCBs (26-45%) from the fish oil, depending on the process used by the business operator. Given that the level of contamination is within the range of the tested untreated fish oil, it is possible to meet EU requirements for these contaminants after decontamination. The CONTAM Panel considered both the evidence provided by one of the business operators and information in the available literature to conclude that the proposed processes do not lead to any detrimental changes in the nature of the fish oil. However, the process can deplete some beneficial constituents (e.g. vitamins). Information was provided to demonstrate the safe disposal of the waste material. The CONTAM Panel concluded that, on the basis of the information submitted by the feed business operators, the proposed decontamination processes to remove dioxins (PCDD/Fs) and DL-PCBs from the fish oil by means of activated carbon and physical filtration were compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.
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http://dx.doi.org/10.2903/j.efsa.2017.5081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010189PMC
December 2017

Risks for public health related to the presence of furan and methylfurans in food.

EFSA J 2017 Oct 25;15(10):e05005. Epub 2017 Oct 25.

The European Commission asked EFSA for a scientific evaluation on the risk to human health of the presence of furan and methylfurans (2-methylfuran, 3-methylfuran and 2,5-dimethylfuran) in food. They are formed in foods during thermal processing and can co-occur. Furans are produced from several precursors such as ascorbic acid, amino acids, carbohydrates, unsaturated fatty acids and carotenoids, and are found in a variety of foods including coffee and canned and jarred foods. Regarding furan occurrence, 17,056 analytical results were used in the evaluation. No occurrence data were received on methylfurans. The highest exposures to furan were estimated for infants, mainly from ready-to-eat meals. Grains and grain-based products contribute most for toddlers, other children and adolescents. In adults, elderly and very elderly, coffee is the main contributor to dietary exposure. Furan is absorbed from the gastrointestinal tract and is found in highest amounts in the liver. It has a short half-life and is metabolised by cytochrome P450 2E1 (CYP2E1) to the reactive metabolite, -but-2-ene-1,4-dialdehyde (BDA). BDA can bind covalently to amino acids, proteins and DNA. Furan is hepatotoxic in rats and mice with cholangiofibrosis in rats and hepatocellular adenomas/carcinomas in mice being the most prominent effects. There is limited evidence of chromosomal damage and a lack of understanding of the underlying mechanism. Clear evidence for indirect mechanisms involved in carcinogenesis include oxidative stress, gene expression alterations, epigenetic changes, inflammation and increased cell proliferation. The CONTAM Panel used a margin of exposure (MOE) approach for the risk characterisation using as a reference point a benchmark dose lower confidence limit for a benchmark response of 10% of 0.064 mg/kg body weight (bw) per day for the incidence of cholangiofibrosis in the rat. The calculated MOEs indicate a health concern. This conclusion was supported by the calculated MOEs for the neoplastic effects.
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http://dx.doi.org/10.2903/j.efsa.2017.5005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009982PMC
October 2017

Assessment of a decontamination process for hydrocyanic acid in linseed intended for use in animal feed.

EFSA J 2017 Oct 4;15(10):e05004. Epub 2017 Oct 4.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process for the enzymatic treatment and subsequent heating of linseed, in order to reduce the amount of hydrocyanic acid (HCN) present as cyanogenic glycosides. Specifically, it is required that the feed decontamination process is compliant with the acceptability criteria specified in the Commission Regulation (EU) 2015/786 of 19 May 2015. With this aim, the CONTAM Panel assessed the data provided by the feed business operator with respect to the efficacy of the process to remove the contaminant from the linseed batches and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. The data enabled the Panel to conclude that in agreement with the literature the process was able to remove HCN by about 90%, and that it is possible to meet the current EU requirements for quality of linseed with respect to HCN, provided the level of contamination of untreated linseed would be within the range of the tested batches. The Panel noted that the amounts of other products formed during the enzymatic process and remaining in the treated material are not of toxicological concern. The experimental data provided by the feed business operator showed that the characteristics of linseed were not adversely affected by the decontamination process. The CONTAM Panel concluded that, on the basis of the information submitted by the feed business operator, the proposed decontamination process to remove HCN from linseed by means of enzymatic release and subsequent evaporation was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.
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http://dx.doi.org/10.2903/j.efsa.2017.5004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009918PMC
October 2017

Depressive-like phenotype induced by prenatal dexamethasone in mice is reversed by desipramine.

Neuropharmacology 2017 Nov 13;126:242-249. Epub 2017 Sep 13.

Department of Neuroscience, Karolinska Institutet, Retzius väg 8, Stockholm S-17177, Sweden. Electronic address:

Exposure to prenatal insults has been associated with an increased risk for neuropsychiatric disorders, including depression, but the mechanisms are still poorly understood. Persistent alterations of the HPA axis feedback mechanism as well as adult impaired neurogenesis are believed to play a relevant role in the etiology of depression. In addition, growing evidence points at epigenetic reprogramming as a key factor. We have previously shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) impairs neurogenesis and leads to late onset of depression-like behavior that does not respond to the SSRI antidepressant fluoxetine (FLX). The aims of this study were to assess the effect of DEX prenatal exposure on the morphology of hippocampal granule neurons and on the expression of genes related to plasticity; and to test whether the SNRI antidepressant desipramine (DMI), unlike FLX, could counteract the effect of prenatal-DEX. C57Bl/6 mice were exposed to DEX (0.05 mg/kg/day) in utero and received intra-hippocampal injection of GFP expressing retroviral vector for labeling of newborn granule cells at eleven months. By twelve months, DEX mice showed depression-like behavior associated with decreased neurogenesis and morphological alterations of the newborn granule cells in the dentate gyrus (DG). Furthermore DEX mice displayed altered expression of genes controlling neurogenesis and neuronal morphology, such as Cdkn1c, p16, TrkB, DISC1 and Reelin. Chronic treatment with DMI led to a significant decrease in immobility time in the forced swim test. In addition, DMI restored neurogenesis, neuronal morphology in the DG, as well as the expression of all related genes. Our results suggest that (1) prenatal DEX induces early and persistent reprogramming effects resulting in altered neurogenesis and neuronal morphology; and (2) DMI treatment reverses DEX-induced depression by restoring the expression of genes relevant to neuronal plasticity.
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http://dx.doi.org/10.1016/j.neuropharm.2017.09.015DOI Listing
November 2017

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed.

EFSA J 2017 Sep 11;15(9):e04718. Epub 2017 Sep 11.

Deoxynivalenol (DON) is a mycotoxin primarily produced by fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 μg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 μg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.
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http://dx.doi.org/10.2903/j.efsa.2017.4718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010102PMC
September 2017

Cerium oxide nanoparticles inhibit differentiation of neural stem cells.

Sci Rep 2017 08 24;7(1):9284. Epub 2017 Aug 24.

Division of Molecular Toxicology, Karolinska Institutet, Stockholm, Sweden.

Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific β3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.
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http://dx.doi.org/10.1038/s41598-017-09430-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570910PMC
August 2017

Gestational Age and Sex Influence the Susceptibility of Human Neural Progenitor Cells to Low Levels of MeHg.

Neurotox Res 2017 Nov 29;32(4):683-693. Epub 2017 Jul 29.

Department of Neuroscience, Karolinska Institutet, Retzius väg 8, SE-171 77, Stockholm, Sweden.

The developing nervous system is highly susceptible to methylmercury (MeHg), a widespread environmental neurotoxic contaminant. A wide range of morphological and functional outcomes have been described; however, there are still open questions regarding the mechanisms behind the developmental neurotoxic effects induced by low-level exposure. In the present study, we have examined the effects of nanomolar concentrations of MeHg on primary fetal human progenitor cells (hNPCs) with special focus on the role played by developmental stage and sex on the neurotoxic outcome. We found that neurospheres derived from earlier gestational time points exhibit higher susceptibility to MeHg, as they undergo apoptosis at a much lower dose (25 nM) as compared to neurospheres established from older fetuses (100 nM). At subapoptotic concentrations (10 nM), MeHg inhibited neuronal differentiation and maturation of hNPCs, as shown by a reduced number of Tuj1-positive cells and a visible reduction in neurite extension and cell migration, associated with a misregulation of Notch1 and BDNF signaling pathways. Interestingly, cells derived from male fetuses showed more severe alterations of neuronal morphology as compared to cells from females, indicating that the MeHg-induced impairment of neurite extension and cell migration is sex-dependent. Accordingly, the expression of the CDKL5 gene, a major factor regulating neurite outgrowth, was significantly more downregulated in male-derived cells. Altogether, gestational age and sex appear to be critical factors influencing in vitro hNPC sensitivity to low levels of MeHg.
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http://dx.doi.org/10.1007/s12640-017-9786-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602033PMC
November 2017

Assessment of a decontamination process for dioxins and dioxin-like PCBs in fish oil by physical filtration with activated carbon.

EFSA J 2017 Jul 31;15(7):e04961. Epub 2017 Jul 31.

Following a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) provided a scientific opinion on the assessment of a decontamination process consisting in the adsorption with activated carbon and physical filtration of fish oil in order to reduce the amount of dioxins (polychlorinated dibenzo--dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs)) and dioxin-like polychlorinated biphenyls (DL-PCBs). All feed decontamination processes must comply with the acceptability criteria specified in the Commission Regulation (EU) 2015/786. The data provided by the feed business operator were assessed with respect to the efficacy of the process and on information demonstrating that the process does not adversely affect the characteristics and the nature of the product. As described in scientific literature, the process was effective in removing PCDD/Fs (84%) and DL-PCBs (55%), and therefore, it is possible to meet the current EU requirements with respect to these contaminants, assuming that the level of contamination of untreated fish oil was within the range of the tested batches. The Panel considered that the reference to information available in published literature was a pragmatic approach to demonstrate that the use of activated carbon adsorption does not lead to any detrimental changes in the nature of the fish oil; however, it was noted that the process could deplete some beneficial constituents (e.g. vitamins). Information was provided to demonstrate the safe disposal of the waste material. The CONTAM Panel concluded that on the basis of the information submitted by the feed business operator the proposed decontamination process to remove dioxins (PCDD/Fs) and DL-PCBs from the fish oil by means of physical filtration with activated carbon, was compliant with the acceptability criteria provided for in Commission Regulation (EU) 2015/786 of 19 May 2015.
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http://dx.doi.org/10.2903/j.efsa.2017.4961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010074PMC
July 2017

Risks for animal health related to the presence of zearalenone and its modified forms in feed.

EFSA J 2017 Jul 31;15(7):e04851. Epub 2017 Jul 31.

Zearalenone (ZEN), a mycotoxin primarily produced by Fusarium fungi, occurs predominantly in cereal grains. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to ZEN and its modified forms in feed. Modified forms of ZEN occurring in feed include phase I metabolites α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), α-zearalanol (α-ZAL), β-zearalanol (β-ZAL), zearalanone (ZAN) and phase II conjugates. ZEN has oestrogenic activity and the oestrogenic activity of the modified forms of ZEN differs considerably. For ZEN, the EFSA Panel on Contaminants in the Food Chain (CONTAM) established no observed adverse effect levels (NOAELs) for pig (piglets and gilts), poultry (chicken and fattening turkeys), sheep and fish (extrapolated from carp) and lowest observed effect level (LOAEL) for dogs. No reference points could be established for cattle, ducks, goats, horses, rabbits, mink and cats. For modified forms, no reference points could be established for any animal species and relative potency factors previously established from rodents by the CONTAM Panel in 2016 were used. The dietary exposure was estimated on 17,706 analytical results with high proportions of left-censored data (ZEN about 60%, ZAN about 70%, others close to 100%). Samples for ZEN were collected between 2001 and 2015 in 25 different European countries, whereas samples for the modified forms were collected mostly between 2013 and 2015 from three Member States. Based on exposure estimates, the risk of adverse health effects of feed containing ZEN was considered extremely low for poultry and low for sheep, dog, pig and fish. The same conclusions also apply to the sum of ZEN and its modified forms.
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http://dx.doi.org/10.2903/j.efsa.2017.4851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009830PMC
July 2017

Presence of free gossypol in whole cottonseed.

EFSA J 2017 Jul 31;15(7):e04850. Epub 2017 Jul 31.

The European Commission asked EFSA to assess information provided by the Spanish Ministry of Agriculture, Food and Environment, on the toxicity of free gossypol in relation to the use of whole cotton seed in feed for ruminants, in particular dairy cows, and, if necessary, to update the previous opinion of the EFSA Panel on Contaminants in the Food Chain (CONTAM) on gossypol as an undesirable substance in animal feed. Gossypol is a polyphenolic compound that exists in a racemic mixture of (+)-gossypol and (-)-gossypol isomers. It occurs in free or (protein-) bound forms in cottonseeds. The most commonly used cottonseeds in feed are from Upland and Pima varieties. The Pima variety is considered more toxic due to a higher content of the (-)-gossypol isomer. Upland whole cottonseeds (WCS) are fed with no further processing (after delinting); Pima varieties normally undergo further processing (grinding or cracking). It is claimed that WCS have a greater retention time in the rumen, which results in an increased detoxifying activity, compared to a shorter ruminal retention time, in the case of cracked cottonseed or cottonseed meal products. Increased erythrocyte fragility has been observed in cows given WCS Upland varieties at similar exposure levels as those resulting from an inclusion rate of 10% of WCS containing gossypol at 7,000 mg/kg in feed - the maximum permitted level of gossypol in WCS suggested by the Spanish Delegation. The information from the Spanish delegation does not differentiate between varieties in their suggestion for an increase in the maximum permitted content of free gossypol for WCS. As both Upland and Pima varieties are grown in the EU and are used for animal feed, both varieties of WCS should be considered. The CONTAM Panel considered it not necessary to update the previous opinion.
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http://dx.doi.org/10.2903/j.efsa.2017.4850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010194PMC
July 2017

Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements.

EFSA J 2017 Jul 27;15(7):e04908. Epub 2017 Jul 27.

EFSA was asked by the European Commission to deliver a scientific opinion on the risks for human health related to the presence of pyrrolizidine alkaloids (PAs) in honey, tea, herbal infusions and food supplements and to identify the PAs of relevance in the aforementioned food commodities and in other feed and food. PAs are a large group of toxins produced by different plant species. In 2011, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) assessed the risks related to the presence of PAs in food and feed. Based on occurrence data limited to honey, the CONTAM Panel concluded that there was a possible health concern for those toddlers and children who are high consumers of honey. A new exposure assessment including new occurrence data was published by EFSA in 2016 and was used to update the risk characterisation. The CONTAM Panel established a new Reference Point of 237 μg/kg body weight per day to assess the carcinogenic risks of PAs, and concluded that there is a possible concern for human health related to the exposure to PAs, in particular for frequent and high consumers of tea and herbal infusions. The Panel noted that consumption of food supplements based on PA-producing plants could result in exposure levels too close (i.e. less than 100 times lower) to the range of doses known to cause severe acute/short term toxicity. From the analysis of the available occurrence data, the CONTAM Panel identified a list of 17 PAs of relevance for monitoring in food and feed. The Panel recommended continuing the efforts to monitor the presence of PAs in food and feed, including the development of more sensitive and specific analytical methods. A recommendation was also issued on the generation of data to identify the toxic and carcinogenic potency of the PAs commonly found in food.
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http://dx.doi.org/10.2903/j.efsa.2017.4908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010083PMC
July 2017

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods.

EFSA J 2017 Apr 20;15(4):e04752. Epub 2017 Apr 20.

Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 μg/kg body weight (bw). However, the uncertainties on the actual exposure in the studies preclude their use for derivation of an acute reference dose (ARfD). Instead, a group ARfD of 0.25 μg/kg bw, applying to TTX and its analogues, was derived based on a TTX dose of 25 μg/kg bw at which no apathy was observed in an acute oral study with mice, applying a standard uncertainty factor of 100. Estimated relative potencies for analogues are lower than that of TTX but are associated with a high degree of uncertainty. Based on the occurrence data submitted to EFSA and reported consumption days only, average and P95 exposures of 0.00-0.09 and 0.00-0.03 μg/kg bw, respectively, were calculated. Using a large portion size of 400 g bivalves and P95 occurrence levels of TTX, with exception of oysters, the exposure was below the group ARfD in all consumer groups. A concentration below 44 μg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC-MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 1 and 25 μg/kg.
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http://dx.doi.org/10.2903/j.efsa.2017.4752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010203PMC
April 2017